We are studying the role of host defense mechanisms in relation to resistance to tumor growth and viral carcinogenesis. For this reason, we are studying two distinctly different antitumor drugs which alter host defenses in an effort to determine what critical changes in RES function produce antitumor activity. The polyanion pyran copolymer possesses antitumor activity against a variety of allogeneic tumors and in addition shows anti-Friend (FLV) leukemia activity. In addition, we are also investigating Tilorone HCl, an oral and systemic antitumor and antiviral agent and its cogeners which similarly affect host resistance but are non-polyanionic compounds. We have investigated these drugs for their effects on host defense mechanisms and are determining whether the antitumor or antitumor virus activity of these compounds is mediated through: 1) direct drug cytotoxic action on tumor cell or tumor virus infected cells, 2) induction of circulating or tissue interferon, 3) enhanced phagocytic and/or killing capacity of phagocytes and related RES cells on target tumor or Friend virus infected cells, 4) through increases of humoral and/or cellular immune response mediated antitumor and/or antiviral activity. Experiments have been designed to determine which if any of the above mechanisms relate to antitumor or antitumor virus activity seen for these compounds. This program, we feel, can permit for the first time rational utilization of specific agents (pyran copolymer fractions, Tilorone and cogeners) which stimulate host defense which alone or in combination with standard chemotherapy can lead to effective clinical agents useful against cancer or oncogenic viruses.